A variety of both neurologic and body disorders involve abnormal amyloid protein aggregation, mitochondrial dysfunction, and/or reduced neuronal activity. Primary among amyloid-aggregating conditions in the brain is Alzheimer's Disease (“AD”), in which the protein β-amyloid (Aβ) is abnormally produced by neurons and deposited both within neurons and outside of neurons. The search for a disease-modifying drug to cure, treat or prevent AD has been ongoing, but failed to develop a drug that can prevent and/or treat AD. Other brain disorders, including those characterized by amyloid protein aggregation, for which therapeutics are currently limited or unavailable, include Mixed AD/Vascular Dementia, Cerebral Amyloid Angiopathy, Hemorrhagic Stroke, Multi-Infarct Dementia, Parkinson's Disease, Lewy Body Dementia, Down's Syndrome, Traumatic Brain Injury, Fronto-Temporal Lobe Dementia, Cerebral Traumatic Encephalopathy, Huntington's Disease, and Prion Diseases (Transmissive Spongiform Encephalopathy, Kuru, and Creutzfeldt-Jakob Disease).
AD and a number of other neurologic conditions are also characterized by mitochondrial dysfunction and/or reduced neuronal activity. Brain mitochondrial dysfunction (low ATP production) occurs in AD, Parkinson's Disease, Huntington's Disease, Amyotrophic Lateral Sclerosis (ALS), mental retardation, stroke, autism, bipolar disorder, schizophrenia, anxiety disorders, mitochondrial encephalomyopathies, epilepsy, migraine headache, and major depression. Reduced neuronal activity is characteristic of AD, stroke and various hyperkinetic disorders such as Huntington's Disease, Dystonia, and Hemiballismus.
In addition to the aforementioned neurologic conditions characterized by amyloid deposition and/or mitochondrial dysfunction, a number of body disorders also involve one or the other of these two characteristics. Abnormal amyloid deposition/aggregation is present in body disorders such as Type II Diabetes, Cardiac Amyloidosis, Systemic AL Amyloidosis, Atherosclerosis, Rheumatoid Arthritis, Aortic Medial Amyloid, and Familial Amyloid Polyneuropathy. As well, mitochondrial dysfunction is characteristic of body disorders such as Type II Diabetes, Cardiovascular Disease (including Atherosclerosis), Chronic Fatigue Syndrome, Cardiomyopathy, Coronary Artery Disease, Fibromyalgia, and Hepatitis C.
Conventional pharmacotherapy has thus far failed to slow or reverse AD adequately, and has minimally-impacted other brain/body conditions characterized by amyloidosis, mitochondrial dysfunction, and/or reduced neuronal activity. There is a need for non-pharmacologic devices, methods, and systems capable of providing effective therapeutic interventions against diseases of the brain and body—all or some having as their common features amyloid deposition, mitochondrial dysfunction, and/or reduced neuronal activity.
In relation to neurologic conditions, the field of “neuromodulation” involves techniques that can modify brain or peripheral neuronal function at one or several levels. These techniques include the following: Direct Current Stimulation (DCS), Deep Brain Stimulation (DBS), Magnetic Stimulation, and Electromagnetic Stimulation (EMS). With the exception of EMS, these neuromodulatory approaches have drawbacks that hinder their ability to address the afore-mentioned neurologic conditions. These drawbacks include (1) limited brain penetration, (2) only a focal brain area being affected by the treatment, (3) being invasive and expensive, (4) requiring clinical visits, and/or (5) having no demonstrated benefit.
In contrast to other neuromodulatory approaches against neurologic conditions, studies in AD transgenic mice and normal mice have shown an ability of EMS to prevent or reverse cognitive impairment. Among other things, these studies demonstrate the ability of EMS to: (1) prevent and reverse brain β-amyloid aggregation/deposition in vitro and in vivo, (2) enhance brain mitochondrial function, and (3) increase brain neuronal activity. Such studies are discussed in G. W. Arendash (2012) Transcranial Electromagnetic Treatment Against Alzheimer's Disease: Why it has the potential to trump Alzheimer's Disease drug development, Journal of Alzheimer's Disease 32: 243-266 (hereafter, “Arendash 2012”). This article is incorporated herein by reference.
Since Arendash (2012) shows that EMS enhances cognition in AD mice through anti-aggregation of amyloid proteins, mitochondrial enhancement, and increase neuronal activity, the many neurologic disorders characterized by aggregated amyloid proteins, mitochondrial dysfunction, and/or reduced neuronal activity all can potentially be improved, reversed or prevented by the use of EMS. Moreover, even normal mice respond to EMS with improved cognitive function, enhanced mitochondrial function and increased neuronal activity, indicating the potential for EMS to benefit normal subjects.
The neuromodulatory approach of EMS has thus far been limited to neurologic disorders. For example, known EMS treatments for AD only teach the use of EMS at a very high frequency and extremely low power (the power is also called the Specific Absorption Rate or “SAR”) levels delivered to the ear, and for only a few seconds per session. Prior EMS work involving AD mice has been limited in providing only a specific set of EMS parameters (i.e., 918 MHz, 0.25 W/kg SAR) and a single EMS modality (i.e., GSM, pulsed and modulated), using only a single EMS-emitting antenna, and only full body treatment. For example, such a method is disclosed in U.S. Patent Publication No. 20120065456, the disclosure of which that is not inconsistent with this disclosure is incorporated herein by reference.
Given the above drawbacks of various neuromodulatory approaches, and the limited nature of the EMS work described above, a need exists for EMS devices, methods, and systems that can provide a range of EMS parameters and modalities for both the body and/or brain. This includes devices, methods, and systems to deliver full body EMS, or restricted EMS to a particular body area (e.g., the heart), and/or restricted to the brain or an area of the brain. For brain conditions/disorders, a need exists for EMS limited to the head via a self-contained device with multiple EMS emitting antennas. Such a need exists not only for such a head-only device against AD, but also against other amyloid-based neurologic conditions, as well as neurologic conditions characterized by mitochondrial dysfunction and/or reduced neuronal activity. In view of the small, but significant, loss of cognitive function/memory during normal aging (commonly called Aged-Associated Memory Impairment, or AAMI), such a head-only method to treat or prevent AAMI would be highly desirable, as would a method that could enhance cognitive function/memory in normal (unimpaired) individuals.